Studies are in progress which are designed to elucidate the molecular and cellular mechanisms which regulate hemopoietic cell differentiation in the human and experimental animal. Specific objectives include the study of regulatory defects in inherited disorders of hemopoietic development in man and studies on the effects of erythropoietin on cell differentiation in vitro. During the past year the isolation of biologically active globin mRNA from human erythroid cells has been accomplished and two complementary methods for assaying globin mRNA for alpha and beta globin chains have been developed. Both tests, the biological activity in the cell-free system, and molecular hybridization with globin cDNA indicate that in certain forms of beta-thalassemia the biological defect is due to a reduced quantity of globin beta mRNA. Precursor hemopoietic cells capable of responding to erythropoietin have been isolated from fetal mice and the nature of the cellular and molecular response studied. It is shown that there is an early stimulation of ribosomal and tRNA followed after about 5 hrs by appearance of globin mRNA (and globin synthesis) as measured both by cell-free system assay and by molecular hybridization.